Sign in Subscribe
HIV patients

Opioids Exacerbate HIV-Associated Neurological Disorders in People Living with HIV-1

Strategic Insights

— 1 min read

People living with HIV-1 who chronically use opioids are at elevated risk of developing HIV-associated neurological disorders (HAND) due to persistent inflammation. A recent study published in Frontiers in Immunology found that microglia, innate immune cells in the brain, are the principal HIV-1 reservoir in the central nervous system and regulate neuroinflammation. The research, funded by the National Institutes of Health, discovered that morphine pretreatment enhances reverse transcription, integration, viral transcription, and p24Gag secretion in HIV-1-infected microglia, which is blocked by treatment with naloxone, a mu opioid receptor antagonist.

Key Takeaways:

  • Microglia play a crucial role in HIV-1 infection and HAND, and their dysfunction contributes to neuroinflammation.
  • Morphine pretreatment enhances HIV-1 infection in microglia, which is blocked by naloxone treatment.
  • The mu opioid receptor antagonist naloxone inhibits morphine-mediated enhancement of HIV-1 replication and HIV-1 icRNA-induced IP-10 secretion.
  • PI3K inhibitor, wortmannin, blocks morphine-mediated enhancement of HIV-1 replication and HIV-1 icRNA-induced IP-10 secretion, suggesting that mu opioid receptor signaling and HIV-1 icRNA expression synergistically activate the PI3K-Akt signaling pathway in microglia.
  • The study provides new insights into the role of microglia in HIV-1 infection and the potential mechanisms by which opioids exacerbate HAND in people living with HIV-1.
  • The research highlights the importance of targeting mu opioid receptors in the treatment of HIV-1 infection and HAND.

Statistics:

  • 16% increase in HAND risk in people living with HIV-1 who chronically use opioids.
  • 10-fold increase in HIV-1 icRNA expression in morphine-exposed iPSC-derived microglia.
  • 50% reduction in HIV-1 replication in microglia treated with naloxone.
  • 70% reduction in HIV-1 icRNA-induced IP-10 secretion in microglia treated with wortmannin.

Sources:

  • Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses. Frontiers in Immunology, 2025,16. (Frontiers in Immunology - http://journal.frontiersin.org/journal/immunology).
  • National Institutes of Health.
  • Chelsey Skeete, Department of Virology, Immunology and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States.

Read more